Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells: Implications for Mastocytosis

Alanazi, SultanUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)

Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells : Implications for Mastocytosis

Background/Aim: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue.Materials and Methods: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells.Results: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7(-) cells were not predominant, suggesting a type of cell death differing from classical apoptosis.Conclusion: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.

Melo, Fabio R.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)fabme873 (author)
Pejler, GunnarSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University(Swepub:slu)49530 (author)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)
Sveriges lantbruksuniversitet

In:Anticancer Research: INT INST ANTICANCER RESEARCH40:5, s. 2525-25360250-70051791-7530

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

By the university: Uppsala University; Swedish University of Agricultural Sciences

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